Antibiotic Spacers in Shoulder Arthroplasty: Comparison of Stemmed and Stemless Implants.

Background: Antibiotic spacers in shoulder periprosthetic joint infection deliver antibiotics locally and provide temporary stability. The purpose of this study was to evaluate differences between stemmed and stemless spacers. Methods: All spacers placed from 2011 to 2013 were identified. Stemless spacers were made by creating a spherical ball of cement placed in the joint space. Stemmed spacers had some portion in the humeral canal. Operative time, complications, reimplantation, reinfection, and range of motion were analyzed. Results: There were 37 spacers placed: 22 were stemless and 15 were stemmed. The stemless spacer population was older (70.9 ± 7.8 years vs. 62.8 ± 8.4 years, p = 0.006). The groups had a similar percentage of each gender (stemless group, 45% male vs. stemmed group, 40% male; p = 0.742), body mass index (stemless group, 29.1 ± 6.4 kg/m2 vs. stemmed group, 31.5 ± 8.3 kg/m2; p = 0.354) and Charlson Comorbidity Index (stemless group, 4.2 ± 1.2 vs. stemmed group, 4.2 ± 1.7; p = 0.958). Operative time was similar (stemless group, 127.5 ± 37.1 minutes vs. stemmed group, 130.5 ± 39.4 minutes). Two stemless group patients had self-resolving radial nerve palsies. Within the stemless group, 15 of 22 (68.2%) underwent reimplantation with 14 of 15 having forward elevation of 109° ± 23°. Within the stemmed group, 12 of 15 (80.0%, p = 0.427) underwent reimplantation with 8 of 12 having forward elevation of 94° ± 43° (range, 30° to 150°; p = 0.300). Two stemmed group patients had axillary nerve palsies, one of which self-resolved but the other did not. One patient sustained dislocation of reverse shoulder arthroplasty after reimplantation. One stemless group patient required an open reduction and glenosphere exchange of dislocated reverse shoulder arthroplasty at 6 weeks after reimplantation. Conclusions: Stemmed and stemless spacers had similar clinical outcomes. When analyzing all antibiotic spacers, over 70% were converted to revision arthroplasties. The results of this study do not suggest superiority of either stemmed or stemless antibiotic spacers

Sixteen years of Collaborative Learning through Active Sense-making in Physics (CLASP) at UC Davis

This paper describes our large reformed introductory physics course at UC Davis, which bioscience students have been taking since 1996. The central feature of this course is a focus on sense-making by the students during the five hours per week discussion/labs in which the students take part in activities emphasizing peer-peer discussions, argumentation, and presentations of ideas. The course differs in many fundamental ways from traditionally taught introductory physics courses. After discussing the unique features of CLASP and its implementation at UC Davis, various student outcome measures are presented showing increased performance by students who took the CLASP course compared to students who took a traditionally taught introductory physics course. Measures we use include upper-division GPAs, MCAT scores, FCI gains, and MPEX-II scores.Comment: Also submitted to American Journal of Physic

Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.

PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches

Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors

Le Certificat de compétence additionnelle en médecine familiale : une enquête descriptive sur le point de vue des médecins de famille sur les pratiques d'amélioration des compétences au Canada

Introduction: The College of Family Physicians of Canada (CFPC) offers the Certificate of Added Competence (CAC) program to designate a family physician with enhanced skills. In 2015, the College expanded its program to introduce enhanced certification in four new domains: Palliative Care, Care of the Elderly, Sports and Exercise Medicine, and Family Practice Anesthesia. In this study, we elicited perceptions from Canadian family physicians with and without the CAC on practice impacts associated with the program. Methods: Active family physicians in Canada with and without CACs were surveyed between November 2019 to January 2020. Descriptive statistics were generated to describe the perceptions of family physicians regarding the CAC program and its impacts on practice. Results: Respondents agreed with several benefits of the program including enhancing the capacity to deliver comprehensive care, alleviating the burden of patient travel by increasing the availability of care in rural and remote communities, and providing opportunities to engage in various collaborative care models and new leadership roles. All respondents perceived CAC holders to pursue the certificate to meet both professional interests and community needs. Conclusions: There is a need for strong and continued investment in systemic practice improvements that incentivize the delivery of comprehensive family medicine practice.Introduction : Le certificat de compétence additionnelle (CCA) accordé par le Collège des médecins de famille du Canada (CMFC) vise à reconnaître un haut niveau de compétences chez un médecin de famille. En 2015, le Collège a élargi le titre de compétences additionnelles à quatre nouveaux domaines : soins palliatifs, soins aux personnes âgées, médecine du sport et de l'exercice, et anesthésie en médecine familiale. Dans cette étude, nous avons recueilli les perceptions de médecins de famille titulaires et non titulaires d’un CCA sur l’influence de pratiques associées au programme de certification. Méthodes : Des médecins de famille actifs au Canada, titulaires et non titulaires du CCA, ont été interrogés entre novembre 2019 et janvier 2020. Des statistiques descriptives ont été générées pour décrire leurs perceptions concernant le Certificat et ses impacts sur la pratique. Résultats : Les répondants s’entendaient pour reconnaître au CCA plusieurs avantages, notamment le fait d'améliorer la capacité des médecins à fournir des soins complets, de leur offrir la possibilité de s'engager dans divers modèles de soins collaboratifs et de nouveaux rôles de leadership, et d'alléger le fardeau des déplacements des patients en augmentant la disponibilité des soins dans les populations rurales et éloignées. Tous les répondants estiment que les médecins recherchent l’obtention de ce titre de compétence pour répondre à la fois à leurs intérêts professionnels et aux besoins de la collectivité. Conclusions : Il faut investir de manière importante et continue dans des améliorations systémiques qui favoriseront une pratique holistique de la médecine familiale

Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate-cancer patients

Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be obtained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer alterations reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and variation in that capacity in DTCs from localized disease. Our analysis lays the foundation for elucidation of the relationship between DTC genomic alterations and progressive prostate cancer

Paradigmatic Approaches to Studying Environment and Human Health: (Forgotten) Implications for Interdisciplinary Research

Copyright © 2013 ElsevierInterdisciplinary research is increasingly promoted in a wide range of fields, especially so in the study of relationships between the environment and human health. However, many projects and research teams struggle to address exactly how researchers from a multitude of disciplinary and methodological backgrounds can best work together to maximize the value of this approach to research. In this paper, we briefly review the role of interdisciplinary research, and emphasize that it is not only our discipline and methods, but our research paradigms, that shape the way that we work. We summarize three key research paradigms - positivism, postpositivism and interpretivism - with an example of how each might approach a given environment-health research issue. In turn, we argue that understanding the paradigm from which each researcher operates is fundamental to enabling and optimizing the integration of research disciplines, now argued by many to be necessary for our understanding of the complexities of the interconnections between human health and our environment as well as their impacts in the policy arena. We recognize that a comprehensive interrogation of research approaches and philosophies would require far greater length than is available in a journal paper. However, our intention is to instigate debate, recognition, and appreciation of the different worlds inhabited by the multitude of researchers involved in this rapidly expanding field

Genetic Discovery and Risk Characterization in Type 2 Diabetes across Diverse Populations

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in th

The maternal and early embryonic transcriptome of the milkweed bug Oncopeltus fasciatus

<p>Abstract</p> <p>Background</p> <p>Most evolutionary developmental biology ("evo-devo") studies of emerging model organisms focus on small numbers of candidate genes cloned individually using degenerate PCR. However, newly available sequencing technologies such as 454 pyrosequencing have recently begun to allow for massive gene discovery in animals without sequenced genomes. Within insects, although large volumes of sequence data are available for holometabolous insects, developmental studies of basally branching hemimetabolous insects typically suffer from low rates of gene discovery.</p> <p>Results</p> <p>We used 454 pyrosequencing to sequence over 500 million bases of cDNA from the ovaries and embryos of the milkweed bug <it>Oncopeltus fasciatus</it>, which lacks a sequenced genome. This indirectly developing insect occupies an important phylogenetic position, branching basal to Diptera (including fruit flies) and Hymenoptera (including honeybees), and is an experimentally tractable model for short-germ development. 2,087,410 reads from both normalized and non-normalized cDNA assembled into 21,097 sequences (isotigs) and 112,531 singletons. The assembled sequences fell into 16,617 unique gene models, and included predictions of splicing isoforms, which we examined experimentally. Discovery of new genes plateaued after assembly of ~1.5 million reads, suggesting that we have sequenced nearly all transcripts present in the cDNA sampled. Many transcripts have been assembled at close to full length, and there is a net gain of sequence data for over half of the pre-existing <it>O. fasciatus </it>accessions for developmental genes in GenBank. We identified 10,775 unique genes, including members of all major conserved metazoan signaling pathways and genes involved in several major categories of early developmental processes. We also specifically address the effects of cDNA normalization on gene discovery in <it>de novo </it>transcriptome analyses.</p> <p>Conclusions</p> <p>Our sequencing, assembly and annotation framework provide a simple and effective way to achieve high-throughput gene discovery for organisms lacking a sequenced genome. These data will have applications to the study of the evolution of arthropod genes and genetic pathways, and to the wider evolution, development and genomics communities working with emerging model organisms.</p> <p>[The sequence data from this study have been submitted to GenBank under study accession number SRP002610 (<url>http://www.ncbi.nlm.nih.gov/sra?term=SRP002610</url>). Custom scripts generated are available at <url>http://www.extavourlab.com/protocols/index.html</url>. Seven Additional files are available.]</p